INFLAMMATORY BOWEL DISEASE (IBD) IS A CONDITION OF CHRONIC INTESTINAL INFLAMMATION ARISING FROM INTERACTIONS BETWEEN GENETIC AND ENVIRONMENTAL FACTORS THAT INDUCE AN ABNORMAL IMMUNE RESPONSE AGAINST MICROBES LIVING IN THE INTESTINAL TRACT KNOWN AS THE GUT MICROBIOTA. RECENT ESTIMATES SUGGEST THAT APPROXIMATELY 3.1 MILLION AMERICANS SUFFER FROM IBD, THE TREATMENT OF WHICH EXCEEDS $14.9 BILLION IN DIRECT COSTS AND LOST PRODUCTIVITY ANNUALLY. IBD IS ALSO ASSOCIATED WITH ABNORMAL, OR DYSBIOTIC, COMMUNITIES OF GUT MICROBES. TARGETING THE GUT MICROBIOTA WITH DIETARY FIBERS, SUCH AS RESISTANT STARCH (RS), HAS GAINED ATTENTION AS A PROMISING MODALITY TO PREVENT AND TREAT GASTROINTESTINAL INFLAMMATION. ALTHOUGH WHOLE GRAINS ARE AN IMPORTANT SOURCE OF DIETARY RS FOR AMERICANS, THE SPECIFIC EFFECTS OF THE RS WITHIN WHOLE GRAIN ON GASTROINTESTINAL HEALTH ARE UNKNOWN. PRELIMINARY STUDIES FROM OUR LAB HAVE IDENTIFIED THAT RS FROM WHOLE-GRAIN SORGHUM [SORGHUM BIOCOLOR (L.)] FLOUR SHOWS PARTICULAR PROMISE AS A WHOLE FOOD APPROACH TO PREVENTING INTESTINAL INFLAMMATION AND/OR DYSBIOSIS.AS THE PROCESS OF ISOLATING STARCH FROM CEREAL GRAINS POTENTIALLY MODIFIES ITS ACCESSIBILITY AND DIGESTION BY THE GUT MICROBIOTA, AND THUS ITS ANTI-INFLAMMATORY POTENTIAL, THIS PROPOSAL LEVERAGES OUR ACCESS TO NEAR-ISOGENIC, LOW-RS, WAXY SORGHUM MUTANTS AND MATCHED PARENTAL SORGHUM VARIETIES TO INVESTIGATE THE EFFECTS OF RS IN A WHOLE FOOD MATRIX ON A MOUSE MODEL OF IBD. FURTHERMORE, OUR MOUSE STUDY WILL USE A NOVEL APPROACH IN WHICH GERM-FREE MICE ARE COLONIZED WITH HUMAN GUT BACTERIA TO STUDY HOW DIETARY COMPONENTS INTERACT WITH HUMAN GUT MICROBES WITHIN A MODEL ANIMAL SYSTEM. THE GOAL OF THESE MOUSE STUDIES IS TO DETERMINE WHETHER RS IS A SPECIFIC COMPONENT OF WHOLE-GRAIN SORGHUM THAT CAN PROTECT AGAINST INTESTINAL INFLAMMATION AND DYSBIOSIS. TO ADDRESS THIS GOAL, WE WILL FIRST ASSESS THE EFFECT OF SORGHUM RS CONSUMPTION ON THE DEVELOPMENT OF IBD IN MICE. WE WILL ALSO MEASURE THE EFFECT OF SORGHUM RS CONSUMPTION ON THE COMPOSITION AND FUNCTION OF THE GUT MICROBIOTA OF MICE. THIS PROJECT ADDRESSES THE AFRI PRIORITY AREA "FOOD SAFETY, NUTRITION, AND HEALTH" BY MECHANISTICALLY EVALUATING A SPECIFIC COMPONENT OF WHOLE GRAINS (RS) THAT IS UTILIZED BY HUMAN GUT MICROBES TO PROMOTE GASTROINTESTINAL HEALTH. OUR PROPOSED AIMS ALSO HIGHLIGHT THE UTILITY OF WHOLE GRAIN SORGHUM AS SOURCE OF HUMAN NUTRITION FOR UNMET AMERICAN DIETARY FIBER NEEDS.